Candida albicans causes oral-cavity disease in a large number of patients: Denture stomatitis, angular chelitis (perleche), leukoplakia, glossitis, dental caries and possibly periodontal disease are a few examples of the oral-cavity disease caused by Candida albicans. Even though mucosal infections are the most common form of candidosis in man, we have very little knowledge about host-Candida (pure culture) interactions at mucosal surfaces and we have almost no information about the mucosal immune mechanisms (innate or acquired) that are responsible for resistance to mucosal candidosis. Recent work from our laboratory demonstrated that C. albicans colonizes the oral cavity of germfree athymic or euthymic mice, but infection (i.e. hyphal penetration of mucosal tissues) was minimal and was observed in keratinized epithelium on the dorsal tongue surface (rhomboid glossitis). Overall, these Candida-monoassociated mice (either athymic or euthymic) show remarkable resistance to mucosal candidosis and provide us with an opportunity to study basic aspects of host-Candida interactions at mucosal surfaces. We will be able to delineate the innate or acquired immune mechanisms that are required for resistance to mucosal candidosis. We will use Candida-monoassociated athymic and euthymic mice to study the following: 1) the role of thymus-dependent cell-mediated immunity in resistance to mucosal candidosis; 2) we will elucidate the number and kinds of leukocytes that infiltrate the lamina propria of germfree athymic and euthymic mice after they are colonized with C. albicans; 3) the number and kind of leukocytes that are depleted from the mucosal lamina propria of Candida-monoassociated mice during the experimental induction of oral candidosis by systemic immunosuppression or by topical treatments that damage the mucosal surfaces; and 4) we will assess the effect of prior colonization of mucosal surfaces by bacteria (normal flora) on the susceptibility of athymic and euthymic mice to mucosal candidosis. These unique, gnotobiotic, athymic and euthymic mice will for the first time not only permit us to study host-Candida interactions on mucosal surfaces, but the models will allow us to delineate the specific mechanisms that are important for innate or acquired (cellular or humoral) resistance to mucosal candidosis.